Perforated tissue matrix

ABSTRACT

The present disclosure relates to tissue matrix products. The products can includes tissue matrices that have holes or perforations located at certain positions to improve certain in vivo functions without substantial loss of strength or other important properties.

This application is a continuation of U.S. patent application Ser. No.16/712,535, filed Dec. 12, 2019, which is a continuation of U.S. patentapplication Ser. No. 15/260,416, filed Sep. 9, 2016 and now U.S. Pat.No. 10,537,665, which claims priority to U.S. Provisional PatentApplication No. 62/217,353, filed Sep. 11, 2015, each of the aboveapplications is incorporated herein by reference in its entirety.

The present disclosure relates generally to acellular tissue matrixproducts, including tissue matrix products having perforations or holesat certain locations.

Surgeons currently use acellular tissue matrix products such asALLODERM® and STRATTICE™, both dermal acellular matrices produced byLIFECELL® CORPORATION (Branchburg, N.J.), for treatment of a variety ofdifferent structural defects. For example, such products can be usefulin abdominal wall repair (e.g., complex hernia repair), breastreconstruction, orthopedic surgery, and neurosurgical applications.

Such tissue matrix products are often provided as flexible sheets ofmaterial that can replace, augment, or alter existing tissues. For someapplications, however, it may be desirable to include holes or openingsin the sheets, for example, to permit more rapid fluid flow across thesheets or to provide sites for securing surgical anchors such assutures, clips, or staples.

Accordingly, the present application provides tissue matrix productshaving preformed holes or perforations. The holes or perforations areprovided in a configuration that provides the desired functionalitywithout sacrificing other properties such as strength and sutureretention.

According to certain embodiments, a tissue matrix product is provided.The product can include a flexible sheet comprising a tissue matrix,wherein the flexible sheet includes a group of holes passing through thetissue matrix, wherein the holes are formed in a pattern comprised of arepeating motif of five holes.

In other embodiments, a tissue matrix comprising a flexible sheetcomprising a tissue matrix is provided. The flexible sheet includes agroup of between 10 and 80 holes passing through the tissue matrix,wherein the flexible sheet comprises a rectangular shape having a widthbetween 10 cm and 30 cm and a length between 10 cm and 30 cm, and theholes have a maximum dimension between about 1.5 mm and 2.5 mm, andwherein the holes are arranged in a pattern such that a uniaxial tensilestrength measured in any direction along the sheet is at least 60% ofthe uniaxial tensile strength of the sheet without the group of holes.

In other embodiments, a tissue matrix including a flexible sheetcomprising a tissue matrix is provided. The flexible sheet includes agroup of between 10 and 80 holes passing through the tissue matrix,wherein the flexible sheet comprises a rectangular shape having a widthbetween 10 cm and 30 cm and a length between 10 cm and 30 cm, and theholes have a maximum dimension between about 1.5 mm and 2.5 mm, andwherein the holes are arranged in a pattern such that a straight linedrawn obliquely across a top or bottom surface of the tissue matrix canpass through no more than three of the holes.

Also provided are methods of treatment including the disclosed products.

BRIEF DESCRIPTION OF THE DRAWINGS

Reference will now be made to exemplary embodiments, examples of whichare illustrated in the accompanying drawings. Wherever possible, thesame reference numbers will be used throughout the drawings to refer tothe same or like parts. The drawings are not necessarily to scale.

FIG. 1 illustrates methods of treatment of an abdominal wall usingtissue matrix products of the present application.

FIG. 2A illustrates a tissue matrix product including holes orperforations, according to certain embodiments.

FIG. 2B illustrates the tissue matrix product of FIG. 2A with variousfeatures highlighted, according to certain embodiments.

FIG. 2C illustrates the tissue matrix product of FIG. 2A with variousfeatures highlighted, according to certain embodiments.

FIG. 3 illustrates a tissue matrix product including holes orperforations, according to certain embodiments.

FIG. 4 illustrates a tissue matrix product including holes orperforations, according to certain embodiments.

FIG. 5 illustrates a motif for use in creating a hole or perforationpattern, according to certain embodiments.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

Reference will now be made in detail to various embodiments of thedisclosed devices and methods, examples of which are illustrated in theaccompanying drawings. Wherever possible, the same reference numberswill be used throughout the drawings to refer to the same or like parts.

In this application, the use of the singular includes the plural unlessspecifically stated otherwise. In this application, the use of “or”means “and/or” unless stated otherwise. Furthermore, the use of the term“including”, as well as other forms, such as “includes” and “included”,is not limiting. Any range described herein will be understood toinclude the endpoints and all values between the endpoints.

The section headings used herein are for organizational purposes onlyand are not to be construed as limiting the subject matter described.All documents, or portions of documents, cited in this application,including but not limited to patents, patent applications, articles,books, and treatises, are hereby expressly incorporated by reference intheir entirety for any purpose.

The present disclosure relates generally to devices for surgicalprocedures and systems and methods relating to such devices. The devicescan be used for tissue augmentation, repair or regeneration of damagedtissue, and/or correction of tissue defects. As such, the devices andmethods discussed herein can be suitable for a wide range of surgicalapplications, such as, for example, abdominal wall repair, prophylactictreatment of post-operative complications (e.g., to prevent hernia,dehiscence, or other post-operative abdominal complications), herniatreatment (e.g., any abdominal or visceral hernia, such as a hiatalhernia, inguinal hernia, parastomal hernia, or midline abdominalhernia). The devices disclosed herein can also be used to treat othertissue sites, including, for example, breasts, connective tissue(tendons, ligaments, or fascia), and to assist in any structural defectcorrection or prevention.

The devices and associated methods discussed herein can include aflexible sheet of biologic material, such as an acellular tissue matrix.Such tissue matrix materials are used for a variety of surgicalapplications and have become an important tool for treating orpreventing many problems associated with trauma, post-operativecomplications, and/or structural defects due to aging, disease,congenital or acquired defects, or iatrogenic problems.

For some surgical procedures, it may be desirable to include holes oropenings in the tissue matrix. For example, in some cases, it isdesirable to place a drainage tube near a surgical site to allowdrainage of fluids, e.g., to prevent formation of seromas or other fluidaccumulations. Drainage of fluid from opposite sides of implantabletissue matrices, however, can be improved by providing holes or fluidpassages through the matrices so that a drainage device located on oneside will collect fluids from both sides of the device.

In addition, properly designed holes or openings can be useful forsecuring the tissue matrices. For example, some tissue matrix materialsare designed to be strong and potentially relatively thick. Accordingly,fixation of such devices to surrounding tissues using conventional meanssuch as sutures, staples, or clips, can sometimes be challenging and/ortime consuming. Therefore, tissue matrices with preformed holes that canbe used for fixation using sutures or other means are desirable.

On the other hand, holes or openings in tissue matrices should beconfigured to prevent unacceptable changes in other materialsproperties. For example, a group of holes in a flexible sheet of tissuematrix must be sized, shaped, and positioned such that the tissue matrixdoes not experience an unacceptable degradation in important mechanicalproperties such as tensile strength, elasticity, burst strength, and/orsuture retention strength. Accordingly, the present application providesimproved tissue matrix products that include a group of holes orperforations that are specially configured to provide the aforementionedadvantages without causing unacceptable alterations in other materialproperties. As used herein, “holes” and “perforations” are usedinterchangeably and will generally refer to any opening that passesthrough a flexible sheet of material from one side to the other.

According to certain embodiments, the present application providestissue products for use in surgical procedures. The tissue products caninclude a flexible sheet 10 (FIGS. 2A-C) comprising a tissue matrix,wherein the flexible sheet includes a group of holes 20 passing throughthe tissue matrix 10. The holes 20 can be placed on the sheet in aspecifically designed pattern. In one embodiment, the holes are placedusing a repeating motif 30 (FIG. 2B).

As used herein “motif” will be understood to refer to any repeatablepattern of holes. Further, the motif need not be repeated exactly, butcan be varied (e.g., by changing dimension of holes or spacing ofholes), so long as one or all of the goals discussed herein are met.

According to other embodiments, the present application provides tissueproducts including a flexible sheet 10 comprising a tissue matrix and agroup of holes 20. The holes 20 are sized and positioned on the flexiblesheet of tissue matrix 10 to maintain a desired tensile strength of thesheet, as compared to a sheet without the group of holes 20.

According to other embodiments, the present application provides tissueproducts including a flexible sheet 10 comprising a tissue matrix and agroup of holes 20. The group of holes are positioned such that thenumber of holes that are aligned along an oblique axis of the sheet isminimized or kept below a certain level. For example, in one embodiment,the holes 20 are arranged in a pattern such that a straight line 80, 81(FIG. 2C) drawn obliquely across a top or bottom surface of the tissuematrix can pass through no more than three of the holes 20.

The devices disclosed herein can be used for treating a variety ofdifferent anatomic sites. For example, FIG. 1 illustrates methods oftreatment of an abdominal wall using tissue matrix products 10 of thepresent application. The methods of treatment are described in moredetail below, but in general, the device 10 can be used to treatportions of the abdominal wall 150, while using the group of holes 20 toallow fluid flow through the devices or to provide a site for fixationusing sutures or other fixation means. Furthermore, as discussed below,the devices 10 can be implanted at a variety of different locations tosupport various anatomic structures and/or treat a variety of differentconditions.

FIGS. 2A-2C illustrate an exemplary tissue matrix product 10 includingholes or perforations, according to certain embodiments. The products 10illustrated in each of FIGS. 2A-2C are identical but include differentreference numerals and markings to facilitate discussion of variousfeatures of the product 10.

The tissue matrix product 10 is illustrated as a two-dimensional view ofa flexible sheet of material. Accordingly, it should be appreciated thatthe flexible sheet will have a length 40 and width 50, and a thickness(not shown). The length 40, width 50, and thickness can be selectedbased on the desired surgical indication, e.g., to provide a sufficientsurface area (measured in terms of the length 40 and width 50) andstructural stability (e.g., based on strength, tensile properties,suture retention, burst strength, etc.). For dermal tissue matrixmaterials, the thickness can vary, but may be between, for example, 0.75mm to 4 mm, 0.75 mm to 1.25 mm, or 1.05 mm to 1.55 mm.

The tissue matrices used to produce the products 10 described herein caninclude a variety of different materials. For example, an acellulartissue matrix or other tissue product can be selected to allow tissueingrowth and remodeling to assist in regeneration of tissue normallyfound at the site where the matrix is implanted. For example, anacellular tissue matrix, when implanted on or into subdermal tissue,fascia, mammary tissue, or other tissue, may be selected to allowregeneration of the tissue without excessive fibrosis or scar formation.In certain embodiments, the devices can be formed from ALLODERM® orSTRATTICE™ (LIFECELL® CORPORATION, BRANCHBURG, N.J.) which are human andporcine acellular dermal matrices, respectively. Alternatively, othersuitable acellular tissue matrices can be used. For example, a number ofbiological scaffold materials as described by Badylak et al., or anyother similar materials, can be used. Badylak et al., “ExtracellularMatrix as a Biological Scaffold Material: Structure and Function,” ActaBiomaterialia (2008), doi:10.1016/j.actbio.2008.09.013. The devicesdescribed herein can be produced from a variety of different human oranimal tissues including human, porcine, ovine, bovine, or other animalstissues.

As stated above, the products 10 can include a group of holes 20 thatcan be sized and positioned to provide a number of desired properties.As illustrated in FIG. 2A, the product 10 includes a total of thirtyholes, but a range in the number of holes can be used, as discussedfurther below. Further, as shown in FIG. 2A, the holes 20 can bepositioned such that a perimeter region 60 is formed in which no holes20 are present. The perimeter region 60 can be sized to allow an areafor passage of sutures or other connection devices and/or to provide anon-perforated section for fixation to tissue such as fascia. Suitablesizes may include 1.5-3 cm, 2-2.5 cm, about 2 cm, 1.5-2.5 cm, or valuesin between. Larger or smaller perimeter regions 60 can be used.

To provide the desired functional properties, the group of holes 20 canbe positioned in specialized patterns. For example, in one embodiment,the group of holes 20 are positioned using a repeating motif 30. Themotif 30 can be selected to allow formation of a desired number of holes20 without unacceptable changes in certain material properties such asstrength or elasticity.

A suitable motif 30 is illustrated in FIGS. 2B, 3, 4, and 5 . As shown,the motif 30 can include five holes 20. In one embodiment the motif 30has a rectangular shape with a hole 31 positioned at each corner of therectangle and one hole 32 positioned at the center of the rectangle.Further, as illustrated in FIG. 5 , the rectangular shape can have arange of suitable sizes, including a width 35 and a length 34 (thelength being double the distance 33 measured along an edge of therectangle from a corner hole 31 to the center hole 32). In variousembodiment the width can be between about 2 and 4 cm, or between about2.5 and 3.5 cm; the length between about 3 and 5 cm, between about 3.5and 4.5 cm; and the distance 33 between about 1.5 and 2.5 cm. In oneembodiment, the width is about 3 cm and the length 34 about 4 cm, butthe width and length can be varied (e.g., scaled at the same ratio orotherwise varied in accordance with the goals described herein).

The motif 30 can be distributed across the sheet of tissue matrix 10 ina variety of patterns. For example, as shown, the motif 30 may bearranged in multiple columns 1, 2, 3, and in rows 11, 12, and, 13. Thenumber of columns 1, 2, 3, and rows may be varied based on the size ofthe product 10 and the specific number of holes 20 desired. For example,the device of FIG. 2B includes three columns, but suitable devices mayinclude between 1 and 10 columns, or any specific number in between. Inaddition, each column or row need not include all five holes of a motif.For example, as shown in FIG. 2B, the motifs at some positions, e.g.,column 1, rows 11 and 13, have four holes of the motif 30, and the motifat the top and bottom of column 2 have only three holes (holes 23 and 22are not part of the motif 30 and are discussed below).

The distances between each column 1, 2, 3, and rows 11, 12, 13 can beselected to produce desired hole spacing. For example, in oneembodiment, the distance between two columns and the size of the motifs30 are selected to provide a spacing pattern that reduces linearalignment of holes 20 along various directions of the sheet. In sodoing, the mechanical strength of the products 10 is maintained.

Of note, as shown in FIG. 2B, the distance between holes of two columns(Lr) differs from the distance (Lm) between the holes 31 at bottomcorners of a motif 30. This variation in distance cause the motifs 30 oftwo different columns 1, 2 to fall out of alignment, so that the motifis not simply repeated, and the alignment of holes is reduced alongoblique axes (81, 83—FIG. 2C).

The products 10 described herein can have a variety of shapes and sizes.For example, each of the flexible sheets of tissue matrix illustrated inFIGS. 2A-2C, 3, and 4 are rectangular, which provides a simple shape foruse in abdominal wall procedures. Furthermore, a rectangular shape canbe trimmed or reshaped based on a specific patient's needs or surgeon'spreferences. It will be appreciated, however, that other shapes can beused including circular, oval, square, triangular, bi-convex, orasymmetric shapes.

The size and shape of each of the holes 20 can also be varied.Generally, however, the holes 20 are sized and shaped to preserve themechanical properties of the sheet of tissue matrix 10, while allowingfluid flow or passage of sutures or other anchors through the holes. Forexample, the holes can be sized such that they have a maximum dimensionbetween about 1.5 mm and 2.5 mm, between about 1.6 and 2.4 mm, between1.7 and 2.3 mm, between 1.8 and 2.2. mm, between 1.9 and 2.1 mm, about 2mm, or any values within the aforementioned ranges.

Further, the holes 20 can be shaped to maintain sheet mechanicalproperties. For example, to prevent excess force due to tensile forcesof sutures passed through a hole 20 or high stress points fromstretching, each hole can have a rounded border (e.g., oval, circular,rounded but asymmetric). In one embodiment, all holes 20 are circularand have a diameter between about 1.5 mm and 2.5 mm, between about 1.6and 2.4 mm, between 1.7 and 2.3 mm, between 1.8 and 2.2. mm, between 1.9and 2.1 mm, about 2 mm, or any values within the aforementioned ranges.

In some cases, the size of the holes, position of holes, and othermechanical properties of the tissue matrix 10 are selected to maintain auniaxial tensile strength of the tissue matrix 10. For example, theproduct can be configured such that a uniaxial tensile strength (asmeasured along an axis parallel to the length of the tissue matrix 10)is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%,or at least 90%, or any values in between versus the uniaxial tensilestrength of a sheet not having the holes 20.

The hole size and shape as well as other sheet properties (e.g.,thickness) can be configured to provide holes that will maintain sutureretention strength if sutures or other fixation devices are passedthrough a hole. For example, the suture retention strength of each hole20 can be configured such that it is at least 60%, at least 70%, atleast 80%, at least 90%, at least 95%, at least 99% or approximately100% of the suture retention strength of a region of the same tissuematrix without a hole 20.

Suture retention can be measured using a simple technique. Specifically,a suture or suture analog (e.g., a steel wire) can be passed through thetissue to form a loop, and tension can be applied until the materialtears. The amount of force (Newtons) needed to tear the tissue is thesuture retention strength. The suture retention strength can be measuredby passing the suture through one of the holes 20 to measure the sutureretention when a hole is used.

In various embodiments, the holes 20 are positioned to minimize orcontrol the number of holes that are linearly aligned along variousdirections. For example, in certain embodiments, the holes 20 arepositioned such that the number of holes that are linearly aligned alongan oblique axis 81, 83 of the flexible sheet 10 is kept below a certainvalue.

As used herein “oblique axis” will be understood to refer to a directionalong the flexible sheet that is parallel to the flat top or bottomsurfaces of the sheet (when the flexible sheet is laid on a flatsurface) but is not parallel to an axis 90 directed along the length 40or an axis 91 directed along the width 50 of the flexible sheet 10.

In some embodiments, the number of holes that can be linearly alignedalong an oblique axis is two or fewer, three or fewer, four or fewer, orfive or fewer.

In addition to the holes 20 being provided in a specified pattern, oneor more additional holes 22, 23 can be included. For example, as shownin FIG. 2B, one hole 22 is located at a bottom 25 of the sheet, andanother hole 23 is located at a top 24 of the sheet. The holes 22, 23are provided to identify for a surgeon where the top 24 and bottom 25 ofthe sheet are located (i.e., identify the orientation of the sheet sothat the surgeon recognizes how the sheet should be aligned whenimplanted in an abdominal wall). In particular, using the pattern setforth in FIGS. 2A-2C, the sheet 10 should be implanted such that theholes 22, 23 are generally aligned with an anatomic axis in ansuperior-inferior (rostral-caudal) direction. It will be appreciated,however, that the holes could be moved to identify a different anatomicdirection for different surgical indications.

FIGS. 2A-2B illustrate one embodiment for a flexible sheet of tissuematrix 10 with holes 20. The sheets 10 illustrated therein, however, maybe modified in other ways. For example, FIGS. 3 and 4 illustrate tissuematrix products 10′, 10″ including holes or perforations, but havingdiffering sizes and differing numbers of holes. It should be understoodthat the size of the products and number of holes may be adjusted basedon the size of the patient, the condition to be treated, or otherfactors determined by a surgeon.

The specific number of holes 20 in the devices 10, 10′, 10″ illustratedcan be varied. For example, a sheet can include between 10 and 80 holespassing through the tissue matrix, between 20 and 40 holes, between 20and 50 holes, between 10 and 30 holes, between 14 and 64 holes, or othervalues in between. Further the sheets can be rectangular and have awidth between 10 cm and 30 cm, between 10 cm and 25 cm, between 20 cmand 25 cm, or any ranges in between. In addition the devices 10, 10′,10″ can have a length between 10 cm and 30 cm, between 15 cm and 30 cm,or between 20 cm and 25 cm.

The products described herein are generally described with reference toacellular tissue matrices, but it will be appreciated that the tissuematrices can be pre-treated with exogenous cells or other therapeuticcomponents prior to or after implantation. Accordingly, the devices caninclude tissue matrix products from which substantially all nativecellular material has been removed, but which include exogenous cellularsources such as stem cells, fibroblasts, platelets, blood cells, orother cell sources.

The devices described herein can be used in a variety of differentsurgical operations, including in operations for treatment of abdominalwall issues. For example, FIG. 1 illustrates implantation of devices 10at a variety of different positions within an abdominal wall. Althoughone of skill in the art will recognize that a certain procedure mayrequire only one of the devices 10 of FIG. 1 , each of the illustratedimplantation locations (as well as others) may be desirable, dependingupon the specific procedure being performed. The illustratedimplantation locations would be recognized by surgeons and can includeonlay 170, inlay 171, retromuscular 172, preperitoneal 173, orintraperitoneal 174, but additional sites can be used.

In some embodiments, the device 10 may also be implanted next to adrainage device 200, such as a drainage bulb, which may include a tubethat passes to a surgical location 220 near an implanted device.

Furthermore, the devices 10 can be implanted during open, laparoscopic,or using any suitable surgical approach. The holes 20 can be used toreceive sutures, clips, staples, or other fixation devices thatfacilitate positioning and securing the device and/or surroundingtissues in place.

The holes 20 can be formed in a variety of ways. For example, in oneembodiment, the holes are produced using a machine press with a cuttingdie selected to include elongated sharpened extensions. The sharpenedextensions can be placed in a desired pattern to cut or puncture holes20 while also including a knife or cutting die to cut the perimeter ofthe device 10. Alternatively the holes can be cut individually, by handor using suitable cutting tools.

1. A tissue matrix product, comprising: a flexible sheet comprising atissue matrix, wherein the flexible sheet includes a group of holespassing through the tissue matrix, wherein the holes are formed in apattern comprising a repeating motif of five holes, the motif repeatingin at least two columns, the flexible sheet including a perimeter regionwhere no holes are present, the perimeter region being sized to allow anarea for passage of sutures or other connection devices or to provide anon-perforated section for fixation to tissue such as fascia.
 2. Theproduct of claim 1, wherein a size of the perimeter region is in a rangefrom 1.5 to 3 cm, in a range from 2 to 2.5 cm, about 2 cm, or in a rangefrom 1.5 to 2.5 cm.
 3. The product of claim 1, wherein the repeatingmotif has a rectangular shape that includes a hole positioned at eachcorner of the rectangular shape and one hole positioned at a center ofthe rectangular shape.
 4. The product of claim 1, wherein therectangular shape has a first dimension and a second dimension such thatthe first dimension is greater than the second dimension.
 5. The productof claim 4, wherein adjacent columns are spaced apart from one anotherby a distance different from the second dimension, wherein the distancedefines an area without holes.
 6. The product of claim 1, wherein theflexible sheet has a rectangular shape.
 7. The product of claim 1,wherein the motif is repeated in at least three columns.
 8. The productof claim 1, wherein the motif is repeated in at least two rows.
 9. Theproduct of claim 8, wherein a distance between each column is greaterthan a distance between each row.
 10. The product of claim 1, whereineach hole has a maximum dimension between about 1.5 mm and 2.5 mm. 11.The product of claim 1, wherein each hole has a rounded border.
 12. Theproduct of claim 1, wherein the tissue matrix comprises an acellulartissue matrix, a dermal tissue matrix, a human tissue matrix, or aporcine tissue matrix.
 13. The product of claim 1, wherein substantiallyall native cellular material has been removed from the tissue matrix.14. The product of claim 1, wherein the suture retention strength of anyhole of the group of holes is at least 80% of the suture retentionstrength of a region of the tissue matrix without the hole.
 15. Theproduct of claim 1, wherein the motif in a first column of the twocolumns is not laterally aligned with the motif in a second column ofthe two columns.
 16. A tissue matrix product, comprising: a flexiblesheet comprising a tissue matrix, wherein the flexible sheet includes agroup of between 10 and 80 holes passing through the tissue matrix,wherein the flexible sheet comprises a rectangular shape having a widthbetween 10 cm and 30 cm and a length between 10 cm and 30 cm, and theholes have a maximum dimension between about 1.5 mm and 2.5 mm, andwherein the holes are arranged in a pattern such that a uniaxial tensilestrength measured in any direction along the sheet is at least 60% ofthe uniaxial tensile strength of a sheet without the group of holes. 17.The product of claim 16, wherein the flexible sheet of tissue matrixwith the group of holes has a uniaxial tensile strength measured in anydirection along the sheet that is at least 70% of the uniaxial tensilestrength of a sheet without the group of holes, or more preferably atleast 80% of the uniaxial tensile strength of a sheet without the groupof holes.
 18. The product of claim 16, wherein the flexible sheetincludes a group of between 14 and 64 holes, a group of between 20 and40 holes, a group of between 20 and 50 holes, a group of between 10 and30 holes, or a group of between 14 and 64 holes.
 19. The product ofclaim 16, wherein the flexible sheet has a width between 10 cm and 25 cmand a length between 15 cm and 30 cm, a width between 15 cm and 25 cmand a length between 15 cm and 30 cm, a width between 10 cm and 20 cmand a length between 10 cm and 20 cm, or a width between 20 cm and 25 cmand a length between 25 cm and 30 cm.
 20. The product of claim 16,wherein the holes have a maximum dimension between about 1.8 mm and 2.5mm or between about 1.8 mm and 2.2 mm.
 21. The product of claim 16,wherein each hole has a rounded border.
 22. The product of claim 16,wherein the tissue matrix comprises an acellular tissue matrix, a dermaltissue matrix, a human tissue matrix, or a porcine tissue matrix. 23.The product of claim 16, wherein substantially all native cellularmaterial has been removed from the tissue matrix.
 24. The product ofclaim 16, wherein the suture retention strength of any one of the holesis at least 80% of the suture retention strength of a region of thetissue matrix without the hole, at least 90% of the suture retentionstrength of a region of the tissue matrix without the hole, or at least95% of the suture retention strength of a region of the tissue matrixwithout the hole.
 25. The product of claim 16, wherein the holes areformed in a pattern comprised of a repeating motif of five holes. 26.The product of claim 25, wherein the repeating motif includes arectangular shape with a hole positioned at each corner of the rectangleand one hole positioned at the center of the rectangle.
 27. The productof claim 24, wherein the motif is repeated in at least two columns or atleast three columns.
 28. The product of claim 27, wherein the motif isrepeated in at least two rows or at least three rows.
 29. The product ofclaim 28, wherein a distance between each column is greater than adistance between each row.